thromboxane-b2 and Pulmonary-Disease--Chronic-Obstructive

Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production.. Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays.. All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8-231.5) pg/ml v 84.0 (70.0-98.5) pg/ml, p < 0.001) and exhaled PGE2 was reduced (93.5 (84.0-105-5) pg/ml v 22.0 (15.0-25.5) pg/ml, p < 0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23).. Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.

Topics: Blood Gas Analysis; Cross-Over Studies; Cyclooxygenase Inhibitors; Dinoprostone; Double-Blind Method; Eicosanoids; Female; Forced Expiratory Volume; Humans; Ibuprofen; Lactones; Leukotriene B4; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Sputum; Sulfones; Thromboxane B2; Vital Capacity

We examined composition of plasma non-esterified fatty acids (NFAs), erythrocyte fatty acids, levels of eicosanoids in patients with asthma and chronic obstructive pulmonary disease (COPD) with different type of the inflammatory response. The results of our study show that asthma and COPD in remission are associated with changes in the composition NFAs of plasma, FA of erythrocytes, level eicosanoid despite the difference in the regulation of immunological mechanisms of systemic inflammation. These changes are characterized by excessive production of arachidonic acid (20:4n-6) and cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) and deficiency of their functional antagonist, eicosapentaenoic acid (20:5n-3). The recognized association between altered fatty acid composition and disorders of the immune mechanisms of regulation of systemic inflammation in COPD and asthma demonstrated the important role of fatty acids and their metabolites in persistence of inflammatory processes in diseases of the respiratory system in the condition of remission.. Izuchen sostav zhirnykh kislot (ZhK) plazmy krovi i membran éritrotsitov, uroven' éĭkozanoidov u bol'nykh bronkhial'noĭ astmoĭ (BA) i khronicheskoĭ obstruktivnoĭ bolezn'iu legkikh (KhOBL) pri raznom tipe vospalitel'noĭ reaktsii. Ustanovleno, chto techenie BA i KhOBL v period remissii, nesmotria na razlichie immunologicheskikh mekhanizmov reguliatsii sistemnogo vospaleniia, soprovozhdaetsia odnonapravlennymi izmeneniiami sostava neéterifitsirovannykh zhirnykh kislot plazmy krovi i ZhK membran éritrotsitov, urovnia éĭkozanoidov, kharakterizuiushchimisia povyshennoĭ produktsieĭ arakhidonovoĭ kisloty (20:4n-6) i ee tsiklooksigenaznykh i lipoksigenaznykh metabolitov (tromboksan V2, leĭkotrien V4) na fone defitsita funktsional'nogo antagonista – éĭkozapentaenovoĭ kisloty (20:5n-3). Obnaruzhennaia assotsiatsiia mezhdu modifikatsieĭ sostava zhirnykh kislot krovi i narusheniem immunnykh mekhanizmov reguliatsii sistemnogo vospaleniia pri KhOBL i BA svidetel'stvuet o vazhnom znachenii zhirnykh kislot i ikh metabolitov v persistentsii vospalitel'nogo protsessa pri zabolevaniiakh bronkholegochnoĭ sistemy v period remissii.

Topics: Adult; Arachidonic Acid; Asthma; Case-Control Studies; Eicosapentaenoic Acid; Female; Humans; Inflammation; Leukotriene B4; Lipoxygenases; Male; Prostaglandin-Endoperoxide Synthases; Pulmonary Disease, Chronic Obstructive; Thromboxane B2

The role of eicosanoids, including leukotrienes (LTs) and prostaglandins (PGs), in chronic obstructive pulmonary disease (COPD) is uncertain. The aim of this study was to investigate whether eicosanoids are measurable in exhaled breath condensate (EBC), a non-invasive method of collecting airway secretions, in patients with stable mild to moderate COPD, and to show possible differences in their concentrations compared with control subjects.. LTB(4), LTE(4), PGE(2), PGD(2)-methoxime, PGF(2alpha), and thromboxane B(2) (TxB(2)) were measured in EBC in 15 healthy ex-smokers, 20 steroid naïve patients with COPD who were ex-smokers, and in 25 patients with COPD who were ex-smokers and who were treated with inhaled corticosteroids. The study was of cross sectional design and all subjects were matched for age and smoking habit.. LTB(4) and PGE(2) concentrations were increased in steroid naïve (LTB(4): median 100.6 (range 73.5-145.0) pg/ml, p<0.001; PGE(2): 98.0 (range 57.0-128.4) pg/ml, p<0.001) and steroid treated patients with COPD (LTB(4): 99.0 (range 57.9-170.5) pg/ml, p<0.001; PGE(2): 93.6 (range 52.8-157.0) pg/ml, p<0.001) compared with control subjects (LTB(4): 38.1 (range 31.2-53.6) pg/ml; PGE(2): 44.3 (range 30.2-52.1) pg/ml). Both groups of patients had similar concentrations of exhaled LTB(4) (p=0.43) and PGE(2) (p=0.59). When measurable, LTE(4) and PGD(2)-methoxime concentrations were similar in COPD patients and controls, whereas PGF(2alpha) concentrations were increased in the former. TxB(2)-LI was undetectable in any of the subjects.. There is a selective increase in exhaled LTB(4) and PGE(2) in patients with COPD which may be relatively resistant to inhaled corticosteroid therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Breath Tests; Cross-Sectional Studies; Dinoprost; Dinoprostone; Female; Forced Expiratory Volume; Humans; Leukotriene B4; Leukotriene E4; Leukotrienes; Male; Middle Aged; Prostaglandin D2; Prostaglandins; Pulmonary Disease, Chronic Obstructive; Thromboxane B2; Vital Capacity

To study the therapeutic mechanism of combination therapy of ligustrazine and nitrendipine in treating patients with chronic obstructive pulmonary disease (COPD).. Thirty COPD patients divided in to 3 groups (10 in each) were treated with ligustrazine, nitrendipine and ligustrazine plus nitrendipine respectively, and the changes of hemorrheologic parameters, plasma endothelin (ET-1), thromboxane A2(TXA2) and platelet-P-selectin (CD62P) before and after treatment were observed.. The combination therapy of ligustrazine and nitrendipine could lower the levels of plasma ET-1, TXA2, CD62P and the hemorrheologic parameters.. Combination of ligustrazine and nitrendipine showed a therapeutic effect better than that of the two drugs used separately. Its effect in lowering pulmonary circulation resistance is related with the lowering of plasma vaso-contrictive factor and the changing of hemorrheologic properties. The integrated traditional Chinese and western medical therapy is valuable in treating COPD.

Topics: Aged; Drug Therapy, Combination; Endothelin-1; Female; Humans; Male; Middle Aged; Nitrendipine; P-Selectin; Pulmonary Disease, Chronic Obstructive; Pyrazines; Thromboxane B2; Vasodilator Agents

To investigate whether platelets are activated during an asthmatic attack and to detect the correlation between platelet activation and severity of bronchial asthma.. Plasma concentration of thromboxane B2(TXB2) and 11-dehydro-TXB2(11-DH-TXB2) and P-selectin (CD 62P) on platelet surface were measured in 44 patients with asthma and in 18 normal individuals using ELISA and FCP. The serum ECP level and pulmonary function were also analysed.. The plasma level of 11-DH-TXB2 and TXB2 and the positive percentage of CD 62P on platelets were significantly increased in patients with acute asthma (n = 28) as compared with the control (n = 18, P < 0.01). The plasma concentration of 11-DH-TXB2 and TXB2 were decreased significanty after the control of asthma. The level of platelet activation was correlated with ECP (r = 0.785, P < 0.05), FEV1% (r = -0.867, P < 0.01) and PEF(r = -0.745, P < 0.05).. These results suggest that there is an abnormal platelet activation in asthmatics, which can reflect the severity of bronchial asthma to a certain extent, although its exact, mechanism is unknown. The platelets secret a wide range of biologically active substances capable of inducing or augmenting the airway inflammatory responses in asthma.

Topics: Adolescent; Adult; Aged; Asthma; Blood Platelets; Blood Proteins; Eosinophil Granule Proteins; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; P-Selectin; Peak Expiratory Flow Rate; Platelet Activation; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Ribonucleases; Thromboxane B2